Structure Therapeutics reports 16.3% weight loss with oral aleniglipron at 44 weeks

Structure Therapeutics reported that its once-daily oral pill aleniglipron produced placebo-adjusted weight loss of 16.3% at 44 weeks in a mid-stage trial, the largest reduction the company has reported for the drug and one it describes as comparable to injectable GLP-1 medicines ^[1].

The Phase 2 ACCESS II study enrolled 85 adults with obesity or overweight, defined as a body mass index above 25, plus at least one weight-related health condition ^[1]. Participants began at 5 mg and titrated over four weeks to target doses of 120 mg, 180 mg or 240 mg ^[1]. At 44 weeks, average weight change from baseline was a loss of 13.6% at 120 mg, 15.3% at 180 mg and 15.0% at 240 mg, compared with a gain of 1.1% for placebo ^[1]. All three dose groups were statistically significant versus placebo, with a p-value below 0.0001 ^[1].

In the ongoing ACCESS open-label extension, participants who took aleniglipron during the earlier 36-week randomized phase and were moved to a maximum dose of 120 mg kept losing weight, reaching up to 16.2%, or 40.5 pounds, at 56 weeks ^[1]. Neither study showed evidence of a weight loss plateau, the company said ^[1][2].

Side effects were consistent with the GLP-1 drug class. The most common were gastrointestinal, and nausea and vomiting were the two most frequent during the titration phase ^[1]. Among ACCESS II participants who reached doses of 120 mg or higher between weeks 28 and 44, there was one discontinuation due to an adverse event, or 3.7% ^[1].

The company has been testing a lower 2.5 mg starting dose to reduce those side effects. With a median follow-up of 20 weeks as of a Feb. 20, 2026 cutoff, the overall rate of discontinuation due to adverse events was 2% in the open-label extension and 3.4% in the aleniglipron arm of a body composition study ^[1]. In that study, participants who started at 2.5 mg and titrated monthly had lost 6.8% of body weight at a median follow-up of 20 weeks ^[1]. The company said starting at 2.5 mg "very meaningfully" reduced discontinuations during titration compared with the 5 mg starting dose used in ACCESS and ACCESS II ^[1]. More than 625 participants have been treated with aleniglipron across all studies, with no off-target events reported to date ^[1].

Julio Rosenstock, MD, of the University of Texas Southwestern Medical Center, who chairs the ACCESS program steering committee, called the data "encouraging—particularly the weight loss from baseline of up to -15.3% vs +1.1% at 180mg in ACCESS II that hopefully will be confirmed in larger, longer-term studies" ^[1].

Why it matters for patients

Aleniglipron is investigational. It has not been approved by the FDA and is not available by prescription ^[1][2].

The drug is being developed as a once-daily oral alternative to injectable GLP-1 medicines ^[1]. The company's comparison to injectable efficacy is not based on a head-to-head trial; none has been reported ^[1].

The figures come from small, mid-stage studies: 85 participants in ACCESS II and 71 in the body composition study ^[1]. Mid-stage results often change when tested in larger Phase 3 trials, so how aleniglipron performs in a registrational program is not yet known. How it compares with approved GLP-1 medicines over longer periods, and whether it helps people maintain weight loss after treatment stops, has not been reported.

What happens next

An end-of-Phase 2 meeting with the FDA was scheduled for the second quarter of 2026 ^[1]. On May 7, 2026, the company said it had received positive feedback and guidance for a Phase 3 program that will start at a 2.5 mg titration dose and evaluate multiple doses ^[2]. Phase 3 initiation was described as on track for the second half of 2026 ^[1] and, more specifically, for the third quarter of 2026 ^[2].

Topline results from the ACCESS open-label extension are expected in the third quarter of 2026, with body composition data and data from a 30-week study in people with type 2 diabetes and obesity expected in the fourth quarter ^[2]. The company also plans a SWITCH study looking at moving patients from an approved injectable GLP-1 to oral aleniglipron for weight maintenance, with data expected in the fourth quarter of 2026 ^[2]. Specific Phase 3 target doses beyond "multiple doses" have not been disclosed ^[2].

Aleniglipron data will be presented at the American Diabetes Association's 86th Scientific Sessions, held June 5-8, 2026 ^[2]. The company reported $1.5 billion in cash, cash equivalents and short-term investments as of March 31, 2026, which it says funds operations through the end of 2028 ^[2].